Acute respiratory distress syndrome (
ARDS), also known as
respiratory distress syndrome (
RDS) or
adult respiratory distress syndrome (in contrast with
IRDSInfant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome caused in premature infants by developmental insufficiency of surfactant production and structural...
) is a serious reaction to various forms of injuries to the
lungThe lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
.
ARDS is a severe
lungThe lung or pulmonary system is the essential respiration organ in air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located in the chest on either side of the heart...
disease caused by a variety of direct and indirect issues. It is characterized by
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
of the lung
parenchymaParenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, from Greek parenkhuma, visceral flesh, from parenkhein, to pour in beside : para-, beside + en-, in + khein, to pour.- In animals :The parenchyma are the...
leading to impaired
gas exchangeGas exchange or respiration takes place at a respiratory surface—a boundary between the external environment and the interior of the body. For unicellular organisms the respiratory surface is governed by Fick's law, which determines that respiratory surfaces must have:*a large surface area*a thin...
with concomitant systemic release of inflammatory mediators causing
inflammationInflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. Inflammation is not a...
,
hypoxemiaHypoxia is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
and frequently resulting in multiple organ failure. This condition is often fatal, usually requiring
mechanical ventilationIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
and admission to an
intensive care unitthumb|220px|ICU roomAn intensive care unit , critical care unit , intensive therapy unit or intensive treatment unit is a specialized department used in many countries' hospitals that provides intensive care medicine...
. A less severe form is called
acute lung injuryAcute lung injury is a diffuse heterogeneous lung injury characterized by hypoxemia, non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage...
(
ALI).
ARDS formerly most commonly signified adult respiratory distress syndrome
to differentiate it from infant respiratory distress syndromeInfant respiratory distress syndrome , also called neonatal respiratory distress syndrome or respiratory distress syndrome of newborn, previously called hyaline membrane disease, is a syndrome caused in premature infants by developmental insufficiency of surfactant production and structural...
in premature infants. However, as this type of pulmonary edema also occurs in children, ARDS
has gradually shifted to mean acute
rather than adult
. The differences with the typical infant syndrome remain.
Historical background
Acute respiratory distress syndrome was first described in 1967 by Ashbaugh et al. Initially there was no definition, resulting in controversy over
incidenceIncidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
and
mortalityDeath is the termination of the biological functions that define a living organism. It refers to both a particular event and to the condition that results thereby. The true nature of the latter has for millennia been a central concern of the world's religious traditions and of philosophical...
. In 1988 an expanded definition was proposed which quantified physiologic respiratory impairment.
In 1994 a new definition was recommended by the American-European Consensus Conference Committee. It had two advantages: 1 it recognizes that severity of pulmonary injury varies, 2 it is simple to use.
ARDS was defined as the ratio of arterial partial oxygen tension (PaO
2) as fraction of inspired oxygen
(FiO2)FiO2, in the field of medicine, is the fraction of inspired oxygen in a gas mixture.The FiO2 is expressed as a number from 0 to 1 .The FiO2 of normal room air is 0.21 ....
below 200 mmHg in the presence of bilateral alveolar
infiltrateInfiltration is the diffusion or accumulation of substances not normal to it or in amounts in excess of the normal. The material collected in those tissues or cells is also called infiltrate.-Classification:...
s on the chest x-ray. These infiltrates may appear similar to those of left ventricular failure, but the cardiac silhouette appears normal in ARDS. Also, the pulmonary capillary wedge pressure is normal (less than 18 mmHg) in ARDS, but raised in left ventricular failure.
A PaO
2/FiO
2 ratio less than 300 mmHg with bilateral infiltrates indicates
acute lung injuryAcute lung injury is a diffuse heterogeneous lung injury characterized by hypoxemia, non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage...
(ALI). Although formally considered different from ARDS, ALI is usually just a precursor to ARDS.
Consensus after 1967 and 1994
ARDS is characterized by:
- Acute onset
- Bilateral infiltrates on chest radiograph sparing costophrenic angles
- Pulmonary artery wedge pressure < 18 mmHg (obtained by pulmonary artery catheter
In medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. Its purpose is diagnostic; it is used to detect heart failure or sepsis, monitor therapy, and evaluate the effects of drugs...
ization), if this information is available; if unavailable, then lack of clinical evidence of left ventricular failure suffices
- if PaO2:FiO2 < 300 mmHg acute lung injury
Acute lung injury is a diffuse heterogeneous lung injury characterized by hypoxemia, non cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage...
(ALI) is considered to be present
- if PaO2:FiO2 < 200 mmHg acute respiratory distress syndrome (ARDS) is considered to be present
Patient presentation and diagnosis
ARDS can occur within 24 to 48 hours of an injury or attack of acute illness. In such a case the patient usually presents with shortness of breath,
tachypneaTachypnea is characterized by rapid breathing.It is not identical with hyperventilation - tachypnea may be necessary for a sufficient gas-exchange of the body, for example after exercise, in which case it is not hyperventilation.Tachypnea differs from hyperpnea in that tachypnea is rapid shallow...
, and symptoms related to the underlying cause, i.e. shock. ARDS is classically associated with hypoxemia, petechiae in the axillae and neurologic abnormalities such as mental confusion.
Long term illnesses can also trigger it, eg malaria. The ARDS may then occur sometime after the onset of a particularly acute case of the infection. See
xray of malarial ARDS.
An
arterial blood gasAn arterial blood gas is a blood test that is performed using blood from an artery. It involves puncturing an artery with a thin needle and syringe and drawing a small volume of blood. The most common puncture site is the radial artery at the wrist, but sometimes the femoral artery in the groin or...
analysis and
chest X-rayIn medicine, a chest radiograph, commonly called a chest x-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
allow formal diagnosis by inference using the aforementioned criteria. Although severe hypoxemia is generally included, the appropriate threshold defining abnormal PaO
2 has never been systematically studied.
Any cardiogenic cause of pulmonary edema should be excluded. This can be done by placing a
pulmonary artery catheterIn medicine pulmonary artery catheterization is the insertion of a catheter into a pulmonary artery. Its purpose is diagnostic; it is used to detect heart failure or sepsis, monitor therapy, and evaluate the effects of drugs...
for measuring the pulmonary artery wedge pressure. However, this is not necessary and is now rarely done as abundant evidence has emerged demonstrating that the use of pulmonary artery catheters does not lead to improved patient outcomes in critical illness including ARDS.
Plain Chest X-rays are sufficient to document bilateral alveolar infiltrates in the majority of cases. While CT scanning leads to more accurate images of the pulmonary parenchyma in ARDS, it has little utility in the clinical management of patients with ARDS, and remains largely a research tool.
Pathophysiology
ARDS is characterized by a diffuse inflammation of lung parenchyma. The triggering insult to the parenchyma usually results in an initial release of cytokines and other inflammatory mediators, secreted by local
epithelialIn biology and medicine, an epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body. Many glands are also formed from epithelial tissue...
and
endothelialThe endothelium is the thin layer of cells that line the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. Endothelial cells line the entire circulatory system, from the heart to the smallest capillary...
cellsThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
.
Neutrophils and some T-lymphocytes quickly migrate into the inflamed lung parynchema and contribute in the amplification of the phenomenon.
Typical histological presentation involves diffuse
alveolarAn alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung, the pulmonary alveoli are spherical outcroppings of the respiratory bronchioles and are the primary sites of gas exchange with the blood. Alveoli are particular to mammalian lungs...
damage and
hyalineThe term hyaline literally refers to a substance with a glass-like appearance.In common medical histopathological usage, hyaline is a substance with a glassy, pink appearance after haematoxylin and eosin staining—most often an acellular, proteinaceous material...
membrane formation in alveolar walls.
Although the triggering mechanisms are not completely understood, recent research has examined the role of inflammation and mechanical stress.
Inflammation
Inflammation alone, as in sepsis, causes endothelial dysfunction, fluid extravasation from the
capillariesCapillaries are the smallest of a body's blood vessels and are part of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
and impaired drainage of fluid from the lungs. Dysfunction of type II pulmonary epithelial cells may also be present, with a concomitant reduction in
surfactantSurfactants are wetting agents that lower the surface tension of a liquid, allowing easier spreading, and lower the interfacial tension between two liquids.- Etymology :The term surfactant is a blend of surface active agent...
production. Elevated inspired oxygen concentration often becomes necessary at this stage, and they may facilitate a '
respiratory burstRespiratory burst is the rapid release of reactive oxygen species from different types of cells....
' in immune cells.
In a secondary phase, endothelial dysfunction causes cells and inflammatory exudate to enter the alveoli. This
pulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the lungs. It leads to impaired gas exchange and may cause respiratory failure. It is due to either failure of the heart to remove fluid from the lung circulation or a direct injury to the lung parenchyma...
increases the thickness of the alveolo-capillary space, increasing the distance the
oxygenOxygen Oxygen Oxygen (acid, literally "sharp", from the taste of acids) and -γενής (-genēs) (producer, literally begetter) is the element with atomic number 8 and represented by the symbol O...
must diffuse to reach
bloodBlood is a specialized bodily fluid that delivers necessary substances to the body's cells — such as nutrients and oxygen — and transports waste products away from those same cells....
. This impairs gas exchange leading to hypoxia, increases the work of breathing, eventually induces
fibrosisFibrosis is the formation or development of excess fibrous connective tissue in an organ or tissue as a reparative or reactive process, as opposed to a formation of fibrous tissue as a normal constituent of an organ or tissue....
of the airspace.
Moreover, edema and decreased surfactant production by type II pneumocytes may cause whole
alveoliAn alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung, the pulmonary alveoli are spherical outcroppings of the respiratory bronchioles and are the primary sites of gas exchange with the blood. Alveoli are particular to mammalian lungs...
to collapse, or to completely flood. This loss of aeration contributes further to the
right-to-left shuntA right-to-left shunt is a cardiac shunt which allows, or is designed to cause, blood to flow from the right heart to the left heart. This terminology is used both for the abnormal state in humans and for normal physiological shunts in reptiles....
in ARDS. As the alveoli contain progressively less gas, more blood flows through them without being oxygenated resulting in massive intrapulmonary shunting.
Collapsed alveoli (and small bronchi) do not allow gas exchange. It is not uncommon to see patients with a PaO
2 of 60 mmHg (8.0 kPa) despite mechanical ventilation with 100% inspired oxygen.
The loss of aeration may follow different patterns according to the nature of the underlying disease, and other factors. In pneumonia-induced ARDS, for example, large, more commonly causes relatively compact areas of alveolar infiltrates. These are usually distributed to the lower
lobesIn anatomy, a lobe is a clear anatomical division or extension that can be determined without the use of a microscope This is in contrast to a lobule, which is a clear division only visible histologically....
, in their posterior segments, and they roughly correspond to the initial infected area.
In sepsis or trauma-induced ARDS, infiltrates are usually more patchy and diffuse. The posterior and basal segments are always more affected, but the distribution is even less homogeneous.
Loss of aeration also causes important changes in lung mechanical properties. These alterations are fundamental in the process of inflammation amplification and progression to ARDS in mechanically ventilated patients.
Mechanical stress
Mechanical ventilationIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
is an essential part of the treatment of ARDS. As loss of aeration (and the underlying disease) progress, the work of breathing (WOB) eventually grows to a level incompatible with life. Thus, mechanical ventilation is initiated to relieve respiratory muscles of their work, and to protect the usually obtunded patient's
airwayFor the Australian television series Airways, see Airways .The airways are those parts of the respiratory system through which air flows, to get from the external environment to the alveoli....
s.
However, mechanical ventilation may constitute a risk factor for the development, or the worsening, of ARDS.
Aside from the infectious complications arising from invasive ventilation with tracheal
intubationIn medicine, intubation refers to the placement of a tube into an external or internal orifice of the body. Although the term can refer to endoscopic procedures, it is most often used to denote tracheal intubation. Tracheal intubation is the placement of a flexible plastic tube into the trachea to...
, positive-pressure ventilation directly alters lung mechanics during ARDS. The result is higher mortality, i.e. through baro-trauma, when these techniques are used.
In 1998, Amato et al.
published a paper showing substantial improvement in the outcome of patients ventilated with lower tidal volumeTidal volume is the lung volume representing the normal volume of air displaced between normal inhalation and exhalation when extra effort is not applied....
s (V
t) (6 mL·kg
-1). This result was confirmed in a 2000 study sponsored by the
NIHThe National Institutes of Health is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical and health-related research. It consists of 27 separate institutes and centers which includes the Office...
. Although both these studies were widely criticized for several reasons, and although the authors were not the first to experiment lower-volume ventilation, they shed new light on the relationship between mechanical ventilation and ARDS.
One opinion is that the forces applied to the lung by the ventilator may work as a lever to induce further damage to lung parenchyma. It appears that
shear stressA shear stress, denoted , is defined as a stress which is applied parallel or tangential to a face of a material, as opposed to a normal stress which is applied perpendicularly.-General shear stress:...
at the
interfaceAn interface is a surface forming a common boundary among two different phases, such as an insoluble solid and a liquid, two immiscible liquids or a liquid and an insoluble gas. The importance of the interface depends on which type of system is being treated: the bigger the quotient area/volume,...
between collapsed and aerated units may result in the breakdown of aerated units, which inflate asymmetrically due to the 'stickiness' of surrounding flooded alveoli. The fewer such interfaces around an alveolus, the lesser the stress.
Indeed, even relatively low stress forces may induce
signal transductionIn biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers,...
systems at the cellular level, thus inducing the release of inflammatory mediators.
This form of stress is thought to be applied by the
transpulmonary pressureTranspulmonary pressure is a term used to describe the difference between the alveolar pressure and the pleural pressure in the lungs. During human ventilation, air flows because of pressure gradients. Pressure in the respiratory system can be measured either in the air spaces of the lungs or in...
(
gradientIn vector calculus, the gradient of a scalar field is a vector field which points in the direction of the greatest rate of increase of the scalar field, and whose magnitude is the greatest rate of change....
) (P
l) generated by the ventilator or, better, its cyclical variations. The better outcome obtained in patients ventilated with lower V
t may be interpreted as a beneficial effect of the lower P
l. Transpulmonary pressurePressure is the force per unit area applied in a direction perpendicular to the surface of an object. Gauge pressure is the pressure relative to the local atmospheric or ambient pressure.- Definition :...
, is an indirect functionIn mathematics, a function is a relation between a given set of elements and another set of elements , which associates each element in the domain with exactly one element in the codomain...
of the V
t setting on the ventilator, and only trial patients with plateau pressures (a surrogate for the actual P
l) were less than 32 cmH2OA centimetre of water is a less commonly used unit of pressure. It is used to measure the central venous pressure, the intracranial pressure while sampling cerebrospinal fluid, as well as determining pressures during mechanical ventilation or in water supply networks...
(3.1 kPa) had improved survival.
The way P
l is applied on alveolar surface determines the shear stress to which lung units are exposed. ARDS is characterized by a usually inhomogeneous reduction of the airspace, and thus by a tendency towards higher P
l at the same V
t, and towards higher
stress on less diseased units.
The inhomogeneity of alveoli at different stages of disease is further increased by the gravitational gradient to which they are exposed, and the different perfusion pressures at which blood flows through them. Finally, abdominal pressure exerts an additional pressure on inferoposterior lung segments, favoring compression and collapse of those units.
The different mechanical properties of alveoli in ARDS may be interpreted as having varying time constants (the product of alveolar compliance × resistance). A long time constant indicates an alveolus which opens slowly during tidal inflation, as a consequence of contrasting pressure around it, or altered water-air interface inside it (loss of surfactant, flooding).
Slow alveoli are said to be 'kept open' using
positive end-expiratory pressureIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
, a feature of modern ventilators which maintains a positive airway pressure throughout the whole respiratory cycle. A higher mean pressure cycle-wide slows the collapse of diseased units, but it has to be weighed against the corresponding elevation in P
l/plateau pressure. Newer ventilatory approaches attempt to maximize mean airway pressure for its ability to 'recruit' collapsed lung units while minimizing the shear stress caused by frequent openings and closings of aerated units.
The
prone position- Word history :The word prone, meaning "naturally inclined to something, apt, liable,", is recorded in English since 1382; the meaning "lying face-down" is first recorded in 1578 but is also referred to as "lying down" or "going prone"....
also reduces the inhomogeneity in alveolar time constants induced by gravity and edema. If clinically appropriate, mobilization of the ventilated patient can assist in achieving the same goal.
Progression
If the underlying disease or injurious factor is not removed, the amount of inflammatory mediators released by the lungs in ARDS may result in a
systemic inflammatory response syndromeIn medicine, systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently in response to infection, but not necessarily so...
(or
sepsisSepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection.
if there is lung infection). The evolution towards shock and/or multiple organ failure follows paths analogous to the pathophysiology of sepsis.
This adds up to the impaired oxygenation which is the central problem of ARDS, as well as to respiratory acidosisRespiratory acidosis is a medical condition in which decreased respiration causes increased blood carbon dioxide and decreased pH ....
, which is often caused by ventilation techniques such as permissive hypercapniaPermissive hypercapnia is hypercapnia, , in respiratory insufficient patients in which oxygenation has become so difficult that the optimal mode of mechanical ventilation is not capable of exchanging enough carbon dioxide...
which attempt to limit ventilator-induced lung injury in ARDS.
The result is a critical illness in which the 'endothelial disease' of severe sepsis/SIRS is worsened by the pulmonary dysfunction, which further impairs oxygen delivery.
General
Acute respiratory distress syndrome is usually treated with mechanical ventilationIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
in the Intensive Care Unit. Ventilation is usually delivered through oro-tracheal intubationIn medicine, intubation refers to the placement of a tube into an external or internal orifice of the body. Although the term can refer to endoscopic procedures, it is most often used to denote tracheal intubation. Tracheal intubation is the placement of a flexible plastic tube into the trachea to...
, or tracheostomyTracheotomy and tracheostomy are surgical procedures on the neck to open a direct airway through an incision in the trachea . They are performed by paramedics, veterinarians, emergency physicians and surgeons...
whenever prolonged ventilation (≥2 weeks) is deemed inevitable.
The possibilities of non-invasive ventilationNon Invasive Ventilation refers to the delivery of mechanical ventilation using a face mask or similar device, rather than an endotracheal tube. A major driving force behind the increasing use of NIV has been the desire to avoid complications caused by invasive ventilation, such as infections and...
are limited to the very early period of the disease or, better, to prevention in individuals at risk for the development of the disease (atypical pneumoniaAtypical pneumonia is a pneumonia not caused by one of the more traditional pathogens. It can be caused by a variety of microorganisms. When developed independently from another disease it is called Primary Atypical Pneumonia ....
s, pulmonary contusionA pulmonary contusion is a contusion of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels...
, major surgery patients).
Treatment of the underlying cause is imperative, as it tends to maintain the ARDS picture.
Appropriate antibioticIn common usage, an antibiotic is a substance or compound that kills or inhibits the growth of bacteria...
therapy must be administered as soon as microbiological cultureA microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...
results are available. EmpiricalThe word empirical denotes information gained by means of observation, experience, or experiment. A central concept in science and the scientific method is that all evidence must be empirical, or empirically based, that is, dependent on evidence or consequences that are observable by the senses...
therapy may be appropriate if local microbiological surveillance is efficient. More than 60% ARDS patients experience a (nosocomial) pulmonary infection either before or after the onset of lung injury.
The origin of infectionAn infection is the detrimental colonization of a host organism by a foreign species. In an infection, the infecting organism seeks to utilize the host's resources to multiply, usually at the expense of the host. The infecting organism, or pathogen, interferes with the normal functioning of the...
, when surgically treatable, must be operated on. When sepsisSepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection.
is diagnosed, appropriate local protocolsA medical guideline is a document with the aim of guiding decisions and criteria regarding diagnosis, management, and treatment in specific areas of healthcare. Such documents have been in use for thousands of years during the entire history of medicine...
should be enacted.
Commonly used supportive therapy includes particular techniques of mechanical ventilation and pharmacological agents whose effectiveness with respect to the outcome has not yet been proven. It is now debated whether mechanical ventilation is to be considered mere supportive therapy or actual treatment, since it may substantially affect survival.
Mechanical ventilation
The overall goal is to maintain acceptable gas exchange and to minimize adverse effects in its application. Three parameters are used: PEEP (positive end-expiratory pressure, to maintain maximal recruitment of alveolar units), mean airway pressure (to promote recruitment and predictor of hemodynamic effects) and plateau pressure (best predictor of alveolar overdistention).
Conventional therapy aimed at tidal volumeTidal volume is the lung volume representing the normal volume of air displaced between normal inhalation and exhalation when extra effort is not applied....
s (Vt) of 12-15 ml/kg. Recent studies have shown that high tidal volumes can overstretch alveoli resulting in volutrauma (secondary lung injury). The ARDS Clinical Network, or ARDSNet, completed a landmark trial that showed improved mortalityMortality rate is a measure of the number of deaths in some population, scaled to the size of that population, per unit time. Mortality rate is typically expressed in units of deaths per 1000 individuals per year; thus, a mortality rate of 9.5 in a population of 100,000 would mean 950 deaths per...
when ventilated with a tidal volume of 6 ml/kg compared to the traditional 12 ml/kg. Low tidal volumes (Vt) may cause hypercapniaPermissive hypercapnia is hypercapnia, , in respiratory insufficient patients in which oxygenation has become so difficult that the optimal mode of mechanical ventilation is not capable of exchanging enough carbon dioxide...
and atelectasisAtelectasis is a medical condition in which the lungs are not fully inflated. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation....
due to their inherent tendency to increase dead space.
Low tidal volume ventilation was the primary independent variable associated with reduced mortality in the NIH-sponsored ARDSnet trial of tidal volume in ARDS. Plateau pressure less than 30 cm H2O was a secondary goal, and subsequent analyses of the data from the ARDSnet trial (as well as other experimental data) demonstrate that there appears to be NO safe upper limit to plateau pressure; that is, regardless of plateau pressure, patients fare better with low tidal volumes (see Hager et al., American Journal of Respiratory and Critical Care Medicine, 2005).
APRV (Airway Pressure Release Ventilation) and ARDS / ALI
Although a particular ventilation mode has yet to be "proven in clinical trials"* more effective than others in treating patients with ARDS, ever increasing empirical evidence and clinical experience is showing that APRVis the primary mode of choice when ventilating a patient with ARDS or ALI (Acute Lung Injury).
Advantages to APRV ventilation include: decreased airway pressures, decreased minute ventilation, decreased dead-space ventilation, promotion of spontaneous breathing, almost 24 hour a day alveolar recruitment, decreased use of sedation, near elimination of neuromuscular blockade and an often positive effect on cardiac output (due to the negative inflection from the elevated baseline with each spontaneous breath).
A patient with ARDS on average spends 8 to 11 days on a mechanical ventilator; APRV may reduce this time significantly.
Positive end-expiratory pressure
Positive end-expiratory pressurePositive end-expiratory pressure is a term used in mechanical ventilation to denote the amount of pressure above atmospheric pressure present in the airway at the end of the expiratory cycle. The equivalent in a spontaneously breathing patient is CPAP...
(PEEP) must be used in mechanically-ventilated patients in order to contrast the tendency to collapse of affected alveoli.
Ideally, a 'perfect' PEEP would match the increased alveolar surface tensionSurface tension is a property of the surface of a liquid. It is what causes the surface portion of liquid to be attracted to another surface, such as that of another portion of liquid .Applying Newtonian physics to the forces that arise due to surface tension accurately predicts many liquid behaviors...
, caused by surfactant deficiency and external pressure (edema), thus restoring a normal time constant in all affected units.
However, because of the cited inherent inhomogeneity, surface tension varies, and so do PEEP requirements for the diseased units. Furthermore, high levels of PEEP may impair venous bloodIn the circulatory system, venous blood is blood returning to the heart . With one exception this blood is deoxygenated and high in carbon dioxide, having released oxygen and absorbed CO
2 in the tissues...
return to the right heartThe heart is a muscular organ found in all vertebrates that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
, although the actual impact of PEEP on hemodynamicsHemodynamics, meaning literally "blood movement" is the study of blood flow or the circulation.All animal cells require oxygen for the conversion of carbohydrates, fats and proteins into carbon dioxide , water and energy in a process known as aerobic respiration...
is still debated.
The 'best PEEP' used to be defined as 'some' cmH2O above the lower inflection point (LIP) in the sigmoidalMany natural processes and complex system learning curves display a history dependent progression from small beginnings that accelerates and approaches a climax over time. For lack of complex descriptions a sigmoid function is often used. A sigmoid curve is produced by a mathematical function...
pressure-volume relationship curve of the lung. Recent research has shown that the LIP-point pressure is no better than any pressure above it, as recruitment of collapsed alveoli, and more importantly the overdistension of aerated units, occur throughout the whole inflation. Despite the awkwardness of most procedures used to trace the pressure-volume curve, it is still used by some to define the minimum PEEP to be applied to their patients. Some of the newest ventilators have the ability to automatically plot a pressure-volume curve. The possibility of having an 'instantaneous' tracing trigger might produce renewed interest in this analysis.
PEEP may also be set empirically. Some authors suggest performing a 'recruiting maneuver' (i.e., a short time at a very high continuous positive airway pressure, such as 50 cmH2O (4.9 kPa), to recruit, or open, collapsed unit with a high distending pressure) and then to increase PEEP to a rather high level before restoring previous ventilation. The final PEEP level should be the one just before the drop in PaO2 (or peripheral blood oxygen saturationHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates, and the tissues of some invertebrates....
) during a step-down trial.
PEEP 'stacks up' to Pl during volume-controlled ventilation. At high levels, it may cause significant overdistension of (and injury to) compliant, aerated units, and higher plateau pressures at the same Vt.
Intrinsic PEEP (iPEEP), or auto-PEEP -- first described by John Marini of St.Paul Regions Hospital -- , is not detected during normal ventilation. However, when ventilating at high frequencies, its contribution may be substantial, both in its positive and negative effects. There are 'underground', unproven claims that the Amato and NIH/ARDS Network studies got a positive result because of the high iPEEP levels reached by spontaneously breathing patients in low-volume assist-control ventilation. Whether or not that is true, it is a fact that iPEEP has been measured in very few formal studies on ventilation in ARDS patients, and its entity is largely unknown. Its measurement is recommended in the treatment of ARDS patients, especially when using high-frequency (oscillatory/jet) ventilation.
A compromise between the beneficial and adverse effects of PEEP is, as usual, inevitable.
Prone position
Distribution of lung infiltrates in acute respiratory distress syndrome is non-uniform. Repositioning into the prone position (face down) might improve oxygenation by relieving atelectasisAtelectasis is a medical condition in which the lungs are not fully inflated. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation....
and improving perfusion. However, although the hypoxemia is overcome there seems to be no effect on overall survival.
Fluid management
Several studies have shown that pulmonary function and outcome are better in patients that lost weight or pulmonary wedge pressure was lowered by diuresisDiuresis is the increased production of urine by the kidney.-Types and causes:The kidney normally produces up to 180 L of "pro-urine" per day, but reabsorbs most of this before entering the calyx of the kidney. No more reabsorption takes place past this point.Polyuria is increased diuresis...
or fluid restriction.
Corticosteroids
A Meduri et al. study has found significant improvement in ARDS using modest doses of corticosteroids. This is probably because of a suppression of ongoing inflammation during the fibroproliferative phase of ARDS. The initial regimen consists of methylprednisoloneMethylprednisolone is a synthetic glucocorticoid drug. It is sold in the USA and Canada under the brand names Phocenta, Medrol, Solu-Medrol and Cadista. It is also available as a generic drug....
2 mg/kg daily. After 3-5 days a response must be apparent. In 1-2 weeks the dose can be tapered to methylprednisolone 0.5-1.0 mg daily. Patients with ARDS do not benefit from high-dose corticosteroids.
The recent NIH-sponsored ARDSnet LAZARUS study of corticosteroids for ARDS demonstrated that they are not efficacious in ARDS.
Nitric oxide
Inhaled nitric oxideNitric oxide or nitrogen monoxide is a chemical compound with chemical formula NO. This gas is an important signaling molecule in the body of mammals, including humans, and is an extremely important intermediate in the chemical industry...
(NO) potentially acts as selective pulmonary vasodilator. Rapid binding to hemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of vertebrates, and the tissues of some invertebrates....
prevents systemic effects. It should increase perfusion of better ventilated areas. There are no large studies demonstrating positive results. Therefore its use must be considered individually.
Almitrine bismesylate stimulates chemoreceptors in carotic and aortic bodies. It has been used to potentiate the effect of NO, presumably by potentiating hypoxia-induced pulmonary vasoconstriction. In case of ARDS it is not known whether this combination is useful.
Surfactant therapy
To date no prospective controlled clinical trialA randomized controlled trial is a type of scientific experiment most commonly used in testing the efficacy or effectiveness of healthcare services or health technologies . RCTs are also employed in other research areas, such as judicial, educational, and social research...
has shown a significant mortality benefit of exogenous surfactant in ARDS.
Complications
Since ARDS is an extremely serious condition which requires invasive forms of therapy it is not without risk. Complications to be considered are:
- Pulmonary: barotrauma
Barotrauma is physical damage to body tissues caused by a difference in pressure between an air space inside or beside the body and the surrounding fluid....
(volutrauma), pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
(PE), pulmonary fibrosis, ventilator-associated pneumoniaVentilator-associated pneumonia is a sub-type of hospital-acquired pneumonia which occurs in people who are on mechanical ventilation through an endotracheal or tracheostomy tube for at least 48 hours. VAP is a medical condition that results from infection which floods the small, air-filled sacs ...
(VAP).
- Gastrointestinal: hemorrhage (ulcer), dysmotility, pneumoperitoneum, bacterial translocation.
- Cardiac: arrhythmias, myocardial dysfunction.
- Renal: acute renal failure
Acute renal failure , also known as acute kidney failure or acute kidney injury, is a rapid loss of renal function due to damage to the kidneys, resulting in retention of nitrogenous and non-nitrogenous waste products that are normally excreted by the kidney...
(ARF), positive fluid balance.
- Mechanical: vascular injury, pneumothorax (by placing pulmonary artery catheter), tracheal injury/stenosis (result of intubation and/or irritation by endotracheal tube.
- Nutritional: malnutrition (catabolic state), electrolyte deficiency.
Epidemiology
The annual incidenceIncidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
of ARDS is 1.5–13.5 people per 100,000 in the general population. Its incidence in the intensive care unitthumb|220px|ICU roomAn intensive care unit , critical care unit , intensive therapy unit or intensive treatment unit is a specialized department used in many countries' hospitals that provides intensive care medicine...
(ICU), mechanically ventilatedIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
population is much higher. Brun-Buisson et al. (2004) reported a prevalence of acute lung injury (ALI) (see below) of 16.1% percent in ventilated patients admitted for more than 4 hours. More than half these patients may develop ARDS.
Mechanical ventilationIn medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows...
, sepsisSepsis is a serious medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection.
, pneumoniaPneumonia is an inflammatory illness of the lung. Frequently, it is described as lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid ....
, shock, aspirationIn medicine, aspiration is the entry of secretions or foreign material into the trachea and lungs.The patient may either inhale the material, or it may be blown into the lungs during positive pressure ventilation or CPR...
, traumaPhysical trauma refers to a physical injury, generally of a considerably severe degree. A trauma patient is someone who has suffered serious and life-threatening physical injury with the potential for secondary complications such as shock, respiratory failure and death.-Common causes:Comprehensive...
(especially pulmonary contusionA pulmonary contusion is a contusion of the lung, caused by chest trauma. As a result of damage to capillaries, blood and other fluids accumulate in the lung tissue. The excess fluid interferes with gas exchange, potentially leading to inadequate oxygen levels...
), major surgerySurgery is a medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, to help improve bodily function or appearance, or sometimes for some other reason...
, massive transfusionsBlood transfusion is the process of transferring blood or blood-based products from one person into the circulatory system of another. Blood transfusions can be life-saving in some situations, such as massive blood loss due to trauma, or can be used to replace blood lost during surgery...
, smoke inhalationSmoke inhalation is the primary cause of death in victims of indoor fires.Smoke inhalation injury refers to injury due to inhalation or exposure to hot gaseous products of combustion...
, drug reaction or overdose, fat emboli and reperfusion pulmonary edema after lung transplantationLung transplantation is a surgical procedure in which a patient's diseased lungs are partially or totally replaced by lungs which come from a donor...
or pulmonary embolectomy may all trigger ARDS. Pneumonia and sepsis are the most common triggers, and pneumonia is present in up to 60% of patients. Pneumonia and sepsis may be either causes or complications of ARDS.
Elevated abdominal pressure of any cause is also probably a risk factor for the development of ARDS, particularly during mechanical ventilation.
The mortality rateMortality rate is a measure of the number of deaths in some population, scaled to the size of that population, per unit time. Mortality rate is typically expressed in units of deaths per 1000 individuals per year; thus, a mortality rate of 9.5 in a population of 100,000 would mean 950 deaths per...
varies from 30% to 85%. Usually, randomized controlled trials in the literature show lower death rates, both in control and treatment patients. This is thought to be due to stricter enrollment criteria. Observational studies generally report 50%–60% mortality.
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